POS0658 TUMOR NECROSIS FACTOR BLOCKERS INDUCED SARCOIDOSIS: DESCRIPTION OF 31 CASES FROM THE FRENCH PHARMACOVIGILANCE DATABASE
Authors: M. Trenec, B. Chretien, N. M. Silva, C. Dolladille, J. Alexandre, A. Dumont, A. Nguyen, H. De Boysson, A. Aouba, S. Deshayes
Journal: Annals of the Rheumatic Diseases (2022)

Background Development of Tumor Necrosis Factor blockers (TNFb) whose drug class has several mechanistic and pharmacologic sub-classes, have improved the management of autoimmune and inflammatory diseases, including sarcoidosis. With their increasing use, paradoxical reactions are described and one of the most frequent is sarcoidosis. However, the description of TNFb-induced sarcoidosis (TIS) remains poor, because reported in few and only short case-series. Objectives We aimed to better describe the clinical spectrum of TIS, and the differential involvement of TNFb sub-classes. Methods French pharmacovigilance database was used to collect data on TIS, excluding patients with previous idiopathic sarcoidosis. Statistical analyses were performed using the Mann-Whitney test for quantitative data and Fisher test for qualitative data. A p value &lt; 0.05 was considered statistically significant. Results Data were obtained from 2002 to 2019 for infliximab, adalimumab, golimumab, certolizumab and etanercept. Thirty-one TIS patients were collected from the database, including 12 women (38.7%). In most cases, TNFb was introduced for ankylosing spondylitis (58%), psoriasis (19.3%) or rheumatoid arthritis (16.1%). Median age at TIS occurrence was 54 [43.5; 61.5] years, with a median time to onset of 24 [6.0; 72.0] months. The most frequent involved TNFb was etanercept (n=21, 67.8%). The two mains clinical TIS manifestations were lymph node (n=27, 87.1%) and lung involvement (n=16, 51.6%). The culprit drug was discontinued in 26 (84%) patients, and a double-barreled inflammatory gun to control both initial and induced disorders was proposed in 19 of them (90.5 %), mostly glucocorticoids (n=13, 68.4%) alone or combined with methotrexate (n=3, 15,8%). Among the 14 patients with the available data, the TIS had completely resolved in 11 (78.6%); for all these lasts, the TNFb was discontinued. No significant differences were observed between the TNFb sub-classes of monoclonal antibodies or fusion proteins, regarding clinical presentation, median time to onset or outcome. Conclusion This second largest case-series shows that TIS are mostly encountered with etanercept, but without any difference in clinical or prognostic implications with the other TNFb-subclasses. References [1]Aggarwal BB, Gupta SC, Kim JH. Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood. 2012 Jan 19;119(3):651–65. [2]Cohen Aubart F, Lhote R, Amoura A, Valeyre D, Haroche J, Amoura Z, et al. Drug-induced sarcoidosis: an overview of the WHO pharmacovigilance database. J Intern Med. 2019 Oct 15; [3]Daïen CI, Monnier A, Claudepierre P, Constantin A, Eschard J-P, Houvenagel E, et al. Sarcoid-like granulomatosis in patients treated with tumor necrosis factor blockers: 10 cases. Rheumatology (Oxford). 2009 Aug;48(8):883–6. [4]Javot L, Tala S, Scala-Bertola J, Massy N, Trenque T, Baldin B, et al. [Sarcoïdosis and anti-TNF: a paradoxical class effect? Analysis of the French Pharmacovigilance system database and literature review]. Therapie. 2011 Apr;66(2):149–54. [5]Massara A, Cavazzini L, La Corte R, Trotta F. Sarcoidosis appearing during anti-tumor necrosis factor alpha therapy: a new ‘class effect’ paradoxical phenomenon. Two case reports and literature review. Semin Arthritis Rheum. 2010 Feb;39(4):313–9. [6]Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet P-Y, Müller-Quernheim J. Sarcoidosis. Lancet. 2014 Mar;383(9923):1155–67. Disclosure of Interests None declared